577-nm high-power optically pumped semiconductor laser is safe and effective in the treatment of inflammatory acne: a prospective, single-center, split-face comparative study.

OBJECTIVE: This study aimed to appraise the efficacy of a 577-nm high-power optically pumped semiconductor laser (HOPSL) for the treatment of inflammatory acne. METHODS: The study included 50 patients with acne vulgaris (inflammatory type), 14 men, and 36 women; patient ages ranged from 16 to 35 years. The left side of the face was treated with a single pass of a 577-nm high-power optically pumped semiconductor laser (HOPSL) every 2 weeks for 3 sessions. The severity of acne examined prior to the first session and 4 weeks after the last session (Investigator's Global Assessment of acne severity, IGA; single lesion count). RESULTS: At baseline, no statistically significant difference in the severity of inflammatory acne lesions between both sides was observed. One month after the final session, a significant improvement (IGA reduction of > 50%) of the overall severity of acne was observed in 49 patients (98%) on the laser-treated side versus 41 (82%) the control side of the face (P < .05). Hence, we found a significant reduction in the mean percentage of inflammatory papules, pustules, and nodules on the laser-treated versus the control side (79.33 vs 56.92, 78.04 vs 43.33, 64.85 vs 21.93%, respectively) (P < 0.05). Side effects in the form of erythema and irritation during sessions were transient and tolerated by the patients. CONCLUSION: The 577-nm high-power optically pumped semiconductor laser is effective and safe for the treatment of inflammatory lesions (papules, pustules, and nodules) in acne patients.

Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer.

PURPOSE: Patients with left-sided breast cancer frequently receive deep inspiration breath-hold (DIBH) radiotherapy to reduce the risk of cardiac side effects. The aim of the present study was to analyze intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice. MATERIAL AND METHODS: Overall, we analyzed 103 patients receiving left-sided breast cancer radiotherapy using a surface-guided DIBH technique. During each treatment session the vertical motion of the patient was continuously measured by a surface guided radiation therapy (SGRT) system and automated gating control (beam on/off) was performed using an audio-visual patient feedback system. Dose delivery was automatically triggered when the tracking point was within a predefined gating window. Intra-breath-hold stability and inter-fraction reproducibility across all fractions of the entire treatment course were analyzed per patient. RESULTS: In the present series, 6013 breath-holds during beam-on time were analyzed. The mean amplitude of the gating window from the baseline breathing curve (maximum expiration during free breathing) was 15.8 mm (95%-confidence interval: [8.5-30.6] mm) and had a width of 3.5 mm (95%-CI: [2-4.3] mm). As a measure of intra-breath-hold stability, the median standard deviation of the breath-hold level during DIBH was 0.3 mm (95%-CI: [0.1-0.9] mm). Similarly, the median absolute intra-breath-hold linear amplitude deviation was 0.4 mm (95%-CI: [0.01-2.1] mm). Reproducibility testing showed good inter-fractional reliability, as the maximum difference in the breathing amplitudes in all patients and all fractions were 1.3 mm on average (95%-CI: [0.5-2.6] mm). CONCLUSION: The clinical integration of an optical surface scanner enables a stable and reliable DIBH treatment delivery during SGRT for left-sided breast cancer in clinical routine.

Treatment of onychomycosis using a 1064-nm diode laser with or without topical antifungal therapy: a single-center, retrospective analysis in 56 patients.

BACKGROUND: Currently available treatment options for onychomycosis such as topical and systemic antifungals are often of limited efficacy, difficult to administer or associated with relevant side effects. Non-ablative laser therapy is proposed to represent a safe alternative without the disadvantages of drugs. Yet, to date, the efficacy of laser therapy for onychomycosis is discussed controversially. Against this background, we performed a systematic retrospective analysis of our clinical experience of 4 years of onychomycosis treatment applying a long-pulsed 1.064-nm diode laser. METHODS: We retrospectively evaluated the records of 56 patients with microscopic and culturally proven onychomycosis affecting a toenail of the hallux and other toes, who had been treated with a long-pulsed 1.064-nm diode laser (FOX, A.C.R. Laser GmbH, Nuremberg) during the time period of July 2013-December 2016 with or without concomitant topical antifungals. Thereof, 27 patients received laser treatment and 29 patients received laser treatment in combination with local antifungals. We conducted a mean of 3.9 laser treatments at 2-6-week intervals. The primary endpoint of our analysis was clinical improvement; secondary endpoints were complete remission of fungal pathogens in fungal culture and in microscopy. RESULTS: Clinical improvement was achieved in 56% of patients treated with laser only after a mean of 4.5 treatments and in 69% of patients treated with laser in combination with topical antifungals after a mean of 3.6 treatments. Cultural healing was detected in 63% of patients treated with laser only after a mean of 5.4 treatments, vs. 86% of patients treated with laser and concomitant topical antifungals after a mean of 4.8 treatments. Microscopic healing (complete healing) with the absence of fungal pathogens was achieved in 11% of patients after a mean of 4.7 treatments with laser only, vs. 21% of patients treated with laser and concomitant topical antifungals after a mean of 4 treatments. No relevant adverse effects were observed. CONCLUSIONS: The 1.064-nm diode laser is an effective and safe option for the treatment of onychomycosis. Of note, the combination with topical antifungals will increase overall treatment efficacy and reduce the time to healing. Particularly, patients with contraindications against systemic antifungals may benefit from this multimodal therapeutic approach. Our data, moreover, suggest that treatment efficacy is positively correlated with the total number of laser treatments.

Polyfunctionality of CD4+ T lymphocytes is increased after chemoradiotherapy of head and neck squamous cell carcinoma.

BACKGROUND: For head and neck squamous cell cancer (HNSCC), standard therapy consists of surgery, radiation, and/or chemotherapy. Antineoplastic immunotherapy could be an option in an adjuvant setting and is already in palliation. A functional immune system is a prerequisite for successful immunotherapy. However, effects of the standard-of-care therapy on the patients' immune system are not fully understood. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from patients with HNSCC (n = 37) and healthy controls (n = 10). PBMC were stimulated with staphylococcal enterotoxin B (SEB). Simultaneous expression of various cytokines was measured in CD4+ and CD8+ T cells by multicolor flow cytometry, and polyfunctional cytokine expression profiles were determined on a single-cell basis. RESULTS: Expression levels of all measured cytokines in CD4+ T cells were higher in patients after chemoradiotherapy (CRT) as compared to untreated HNSCC patients or normal controls. After CRT, the frequency of polyfunctional CD4+ T cells, which simultaneously expressed multiple cytokines, was significantly increased as compared to untreated patients (p < 0.01). CONCLUSION: CRT increases polyfunctionality of CD4+ T cells in HNSCC patients, suggesting that standard-of-care therapy can promote immune activity in immune cells. These polyfunctional CD4+ T cells in the blood of treated HNSCC patients are expected to be responsive to subsequent immunotherapeutic approaches.

Feasibility of 6-month maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck.

BACKGROUND: Close resection margins < 5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article. METHODS: Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m(2), days 1-5 and days 29-33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m(2), days 1-5 + days 29-33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m(2) followed by weekly doses of 250 mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500 mg/m(2) every 2 weeks for 6 months. RESULTS: Of the 55 patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3 months and 63 % at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients. CONCLUSION: Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5 months is moderate.

[Current therapy of hepatocellular carcinoma with special consideration of new and multimodal treatment concepts]. / Aktuelle Therapie des hepatozellulären Karzinoms unter besonderer Berücksichtigung neuer und multimodaler Therapiekonzepte.

The incidence of hepatocellular carcinoma (HCC) is increasing worldwide due to the growing number of hepatitis C related HCCs. In more than 80% of the patients, HCC arises in a cirrhotic liver. Furthermore, more than half of the patients have an advanced Child-Pugh score or an inoperable tumor stage at the initial diagnosis. Recommendations for the treatment of HCC by national and international guidelines rely on the BCLC ("Barcelona Clinic for Liver Cancer") algorithm. Depending on the stage of liver function and tumor disease it recommends resection, liver transplantation, radiofrequency thermal ablation (RFA), transarterial chemoembolisation (TACE), systemic therapy with sorafenib or best supportive care, but does neither take into consideration combination of therapies nor new therapy modalities. However, there is increasing evidence that combinations i. e. sorafenib with TACE or combination of locoregional techniques enhance effectivity and tumor control compared to monotherapies. TACE with drug-eluting beads, selective internal radiotherapy (SIRT) and new locoregional therapy procedures like microwave ablation (MWA) are further promising therapeutic approaches. Patients with HCC should be discussed in a local tumor board in order to provide the optimal and most individual way of treatment.

[Radiation-induced Favre-Racouchot disease]. / Strahleninduzierter Morbus Favre-Racouchot.

A 71-year-old man presented with disfiguring skin changes of the nose and cheek. The patient had undergone a surgery of a malignant melanoma of the right paranasal sinus and then 5 months later received radiation therapy with 60 Gy total dose to the endonasal area. Physical examination revealed elastosis, open and closed comedones, and cysts in the field of radiation exposure. Taking in account the exclusive affection of the irradiated skin, we diagnosed a radiation-induced Favre-Racouchot disease. We recommended topical treatment with vitamin A derivatives in combination with physical comedo extraction.

Long-term outcome after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer and predictive factors for a pathologic complete remission : results of a multivariate analysis.

BACKGROUND: An earlier published series of neoadjuvant radiochemotherapy (NRT-CHX) in locally advanced noninflammatory breast cancer (LABC) has now been updated with a follow-up of more than 15 years. Long-term outcome data and predictive factors for pathologic complete response (pCR) were analyzed. PATIENTS AND METHODS: During 1991-1998, 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes combined with an electron boost in 214 cases afterwards or-in case of breast conservation-a 10-Gy interstitial boost with (192)Ir afterloading before EBRT. Chemotherapy was administered prior to RT in 192 patients, and concomitantly in 113; 10 patients received no chemotherapy. The update of all follow-up ended in November 2011. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX, and the time interval between end of RT and surgery were examined in multivariate terms with pCR and overall survival as end point. RESULTS: The total pCR rate after neoadjuvant RT-CHX reached 29.2%, with LABC breast conservation becoming possible in 50.8% of cases. In initially node-positive cases (cN+), a complete nodal response (pN0) after NRT-CHX was observed in 56% (89/159). The multivariate analysis revealed that a longer time interval to surgery increased the probability for a pCR (HR 1.17 [95% CI 1.05-1.31], p < 0.01). However, in large tumors (T3-T4) a significantly reduced pCR rate (HR 0.89 [95% CI 0.80-0.99], p = 0.03) was obtained. Importantly, pCR was the strongest prognostic factor for long-term survival (HR 0.28 [95% CI 0.19-0.56], p < 0.001). CONCLUSION: pCR identifies patients with a significantly better prognosis for long-term survival. However, a long time interval to surgery (> 2 months) increases the probability of pCR after NRT-CHX.

Pitfalls in radiation oncology. "Myocardial metastasis" in PET-CT after palliative radiation treatment of the left 5th rib.

BACKGROUND: Positron emission tomography-computed tomography (PET-CT) is a useful diagnostic tool to detect metastases in patients with malignancy. False positives have been reported in cases of inflammation and tissue regeneration. CASE REPORT: Over a period of 2 years, a 32-year-old woman with hepatocellular carcinoma and multiple bone metastases received three treatments of radiation therapy to a bone metastasis in the 5th left rib. Restaging with [18F]fluorodeoxyglucose (FDG) PET-CT showed increased uptake within the cardiac apex highly suspicious for a myocardial metastasis. Because the patient was asymptomatic, additional magnetic resonance imaging (MRI) of the heart was performed demonstrating radiation-associated changes but no evidence for metastases. CONCLUSION: PET-CT is a well-established diagnostic tool in metastatic diseases but its results should always be correlated with the clinical picture of the patient and previous treatments to rule out false positives.

Breast cancer in the lower jaw after reconstructive surgery with a pectoralis major myocutaneous flap (PMMC) -- a case report.

For head and neck as well as for oromaxillofacial surgery, the use of the pectoralis major myocutaneous (PMMC) flap is a standard reconstructive technique after radical surgery for cancers in this region. We report to our knowledge for the first development of breast cancer in the PMMC flap in a 79 year old patient, who had undergone several operations in the past for recurring squamous cell carcinoma of the jaw. The occurrence of a secondary malignancy within the donor tissue after flap transfer is rare, but especially in the case of transferred breast tissue and the currently high incidence of breast cancer theoretically possible. Therefore preoperative screening mammography seems advisable to exclude a preexisting breast cancer in female patients undergoing such reconstruction surgery. Therapy for breast cancer under these circumstances is individual and consists of radical tumor resection followed by radiation if applicable and a standard systemic therapeutic regimen on the background of the patients individual prognosis due to the primary cancer.

[Case-based interactive PACS learning: introduction of a new concept for radiological education of students]. / Fallbasiertes interaktives "PACS-learning": Vorstellung eines neuen studentischen Lehrkonzepts für die Radiologie.

PURPOSE: Medical curricula are currently being reformed in order to establish superordinated learning objectives, including, e.g., diagnostic, therapeutic and preventive competences. This requires a shifting from traditional teaching methods towards interactive and case-based teaching concepts. Conceptions, initial experiences and student evaluations of a novel radiological course Co-operative Learning In Clinical Radiology (CLICR) are presented in this article. MATERIALS AND METHODS: A novel radiological teaching course (CLICR course), which combines different innovative teaching elements, was established and integrated into the medical curriculum. Radiological case vignettes were created for three clinical teaching modules. By using a PC with PACS (Picture Archiving and Communication System) access, web-based databases and the CASUS platform, a problem-oriented, case-based and independent way of learning was supported as an adjunct to the well established radiological courses and lectures. Student evaluations of the novel CLICR course and the radiological block course were compared. RESULTS: Student evaluations of the novel CLICR course were significantly better compared to the conventional radiological block course. Of the participating students 52% gave the highest rating for the novel CLICR course concerning the endpoint overall satisfaction as compared to 3% of students for the conventional block course. The innovative interactive concept of the course and the opportunity to use a web-based database were favorably accepted by the students. Of the students 95% rated the novel course concept as a substantial gain for the medical curriculum and 95% also commented that interactive working with the PACS and a web-based database (82%) promoted learning and understanding. CONCLUSION: Interactive, case-based teaching concepts such as the presented CLICR course are considered by both students and teachers as useful extensions to the radiological course program. These concepts fit well into competence-oriented curricula.

Trimodal therapy in squamous cell carcinoma of the esophagus.

Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.

Do insulin-like growth factor associated proteins qualify as a tumor marker? Results of a prospective study in 163 cancer patients.

OBJECTIVE: Insulin-like growth factor (IGF)-1, -2 and Insulin like growth factor binding proteins (IGFBP) are involved in the proliferation and differentiation of cells. It has never been evaluated, if the IGF-system can serve as a tumor marker in neoplasms. METHODS: In our prospective study 163 patients with colorectal cancer (22), prostate cancer (21), head and neck tumors (17), lymphomas (20), lung cancer (34) and other entities (49) were analysed for their IGF and IGFBP serum levels at the beginning and the end of radiotherapy and compared to 13 healthy people. Subgroups of patients with local tumor disease versus metastatic disease, primary and recurrent therapy and curative versus palliative therapy were compared. RESULTS: The serum levels of IGF-2 were significantly elevated in patients with prostate and colorectal cancer. However, sensitivity and specificity were only 70%. IGFBP-2 serum levels were elevated in patients with head and neck tumors. Again sensitivity and specificity were only 73%. A difference between local disease and metastatic disease could not be found. A difference between IGF serum levels before and after radiotherapy could not be detected. CONCLUSION: The IGF-system cannot serve as a new tumor marker. The detected differences are very small, sensitivity and specificity are too low. IGF measurement is not useful for the evaluation of the success of radiotherapy in malignancies.

[Multimodal therapy in locally advanced gastric cancer]. / Multimodale Therapie beim lokal fortgeschrittenen Magenkarzinom.

Locally advanced gastric cancers are characterized by poor prognosis. Clinical outcome can be improved if surgery becomes part of a multimodal treatment approach. The purpose of neoadjuvant treatment includes downsizing of the primary tumor, improvement of the T- and N- categories, and early therapy of micrometastasis. Several controlled clinical trials showed that neoadjuvant chemotherapy as well as neoadjuvant combined radio-chemotherapy, especially for tumors of the gastroesophageal junction, can improve the rate of primary R0 resections, relapse-free survival, and overall survival. While patients with locally advanced tumors clearly benefit from this strategy, the approach is still controversial in patients with early stage disease. Nonresponders do not benefit from neoadjuvant therapy. Therefore, response evaluation and response prediction are of great importance. After successful neoadjuvant chemotherapy, patients should undergo gastrectomy with D(2)-lymphadenectomy because of a high probability of lymph node metastasis. This article summarizes current developments in this field.

Dendritic cell generation and CD4+ CD25high FOXP3+ regulatory t cells in human head and neck carcinoma during radio-chemotherapy.

BACKGROUND: Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown. METHODS: For DC generation, CD14⊃+ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4⊃+CD25⊃highFOXP3⊃+ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry. RESULTS: In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients. CONCLUSION: The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.

In vitro chemosensitivity of head and neck cancer cell lines.

BACKGROUND: Systemic treatment of head and neck squamous cell carcinoma (HNSCC) includes a variety of antineoplastic drugs. However, drug-resistance interferes with the effectiveness of chemotherapy. Preclinical testing models are needed in order to develop approaches to overcome chemoresistance. - METHODS: Ten human cell lines were obtained from HNSCC, including one with experimentally-induced cisplatin resistance. Inhibition of cell growth by seven chemotherapeutic agents (cisplatin, carboplatin, 5- fluorouracil, methotrexate, bleomycin, vincristin, and paclitaxel) was measured using metabolic MTT-uptake assay and correlated to clinically-achievable plasma concentrations. - RESULTS: All drugs inhibited cell growth in a concentration-dependent manner with an IC50 comparable to that achievable in vivo. However, response curves for methotrexate were unsatisfactory and for paclitaxel, the solubilizer cremophor EL was toxic. Cross-resistance was observed between cisplatin and carboplatin. - CONCLUSION: Chemosensitivity of HNSCC cell lines can be determined using the MTT-uptake assay. For DNA-interfering cytostatics and vinca alkaloids this is a simple and reproducible procedure. Determined in vitro chemosensitivity serves as a baseline for further experimental approaches aiming to modulate chemoresistance in HNSCC with potential clinical significance.

Fulminant staphylococcus lugdunensis septicaemia following a pelvic varicella-zoster virus infection in an immune-deficient patient: a case report.

INTRODUCTION: the deadly threat of systemic infections with coagulase negative Staphylococcus lugdunensis despite an appropriate antibiotic therapy has only recently been recognized. The predominant infectious focus observed so far is left-sided native heart valve endocarditis, but bone and soft tissue infections, septicaemia and vascular catheter-related bloodstream infections have also been reported. We present a patient with a fatal Staphylococcus lugdunensis septicaemia following zoster bacterial superinfection of the pelvic region. case presentation: a 71-year old male diagnosed with IgG kappa plasmocytoma presented with a conspicuous weight loss, a hypercalcaemic crisis and acute renal failure. After initiation of haemodialysis treatment his condition improved rapidly. However, he developed a varicella-zoster virus infection of the twelfth thoracic dermatome requiring intravenous acyclovir treatment. Four days later the patient presented with a fulminant septicaemia. Despite an early intravenous antibiotic therapy with ciprofloxacin, piperacillin/combactam and vancomycin the patient died within 48 hours, shortly before the infective isolate was identified as Staphylococcus lugdunensis by polymerase chain reaction. CONCLUSION: despite S. lugdunensis belonging to the family of coagulase-negative staphylococci with an usually low virulence, infections with S. lugdunensis may be associated with an aggressive course and high mortality. This is the first report on a Staphylococcus lugdunensis septicaemia following a zoster bacterial superinfection of the pelvic region.

Identification of candidate genes with pro-apoptotic properties by functional screening of randomly fragmented cDNA libraries.

The sequences of many genomes are available; therefore, relevant methods are needed for rapid and efficient identification of functional genes. The ability of tumour cells to resist apoptosis induced by anticancer agents may decide about the success or failure of tumour elimination. Although the CD95-signaling pathway is functional in tumour cells, the increased resistance of tumour cells to CD95-mediated apoptosis has been widely reported. In order to identify genes that might determine the response of tumour cells to CD95-mediated apoptosis, we modified the conventional technical knock out (TKO) strategy for isolation of genes that function in CD95-mediated apoptosis. Due to the fact that multiple different plasmids are usually introduced into the same cells, the effectiveness of the conventional TKO strategies is low. To overcome this obstacle, we replaced the conventional TKO strategy (based on stably expressed randomly fragmented cDNA libraries) with a multi-cycle selection procedure (based on transiently expressed randomly fragmented cDNA libraries with multi-cycle selection). Using this approach we could rapidly and significantly identify small numbers of antisense mRNA molecules, whose re-introduction into different tumour types confirmed their ability to block the pro-apoptotic function of their cognate genes. Thus, our modified TKO strategy provides a generally applicable procedure for the identification of functional genes with pro-apoptotic properties that may be clinically relevant to tumour therapy.

Evaluation of the tissue toxicity of antiseptics by the hen's egg test on the chorioallantoic membrane (HETCAM).

BACKGROUND: Antiseptics are frequently used for the prophylaxis and treatment of local infections of chronic wounds. Whereas local antiseptics in general have a positive effect on wound healing an uncritical use may impair wound healing due to toxic side effects. OBJECTIVE: We sought to assess the vascular irritation potential of different antiseptic solutions and ointments commonly used for short and long term application as a measure of tissue toxicity. METHOD: The vascular irritation was evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on the vessels of a mucous membrane were directly assessed by stereomicroscopic observation in vivo. RESULTS: Severe CAM irritation was observed after short-term applications of 1% octenidin-2HCl (Octenisept), 72% isopropanol (Cutasept), 0.35% chloroxylenol (Dettol) and 10% PVP-I ointment (Betaisodona). Medium irritations were observed for 10% PVP-I solution (Betaisodona), 3% lysosomal PVP-I ointment (Repithel), 1.8% cadexomer-iodine ointment (Iodosorb) and 1% cadexomer-iodine pellets (Iodosorb). Finally, slight irritations were observed for 1% PVP-I solution (Betaisodona), 0.1% polyhexanid plus betain (Prontosan) and 1% silver-sulfadiazine ointment (Flammazine), whereas 0.04% polyhexanid solution (Lavanid), washings from sterile maggots of Lucilia sericata and filtrated enzymes from Clostridium histolyticum (Iruxol-N) showed no effects of irritation. In the long-term approaches, no vascular irritations were found for polyhexanid, washings from Lucilia sericata and enzyme filtrations from Clostridium histolyticum. CONCLUSION: The vascular injuries caused by the studied antiseptics are an indirect indicator of their tissue toxicity. Strikingly, even therapeutic substances, which have been regarded as safe in their application for the treatment of chronic wounds in clinical studies, showed severe irritations on the CAM. We suggest that agents with no or low irritation potential on the CAM should be preferred in the clinical practice in order to obtain optimal results.